Discovery of potent and selective agonists for the free fatty acid receptor 1 (FFA(1)/GPR40), a potential target for the treatment of type II diabetes.
A series of 4-phenethynyldihydrocinnamic acid agonists of the free fatty acid receptor 1 (FFA(1)) has been discovered and explored. The preferred compound 20 (TUG-424, EC(50) = 32 nM) significantly increased glucose-stimulated insulin secretion at 100 nM and may serve to explore the role of FFA(1) in metabolic diseases such as diabetes or obesity.
Christiansen
Elisabeth
E
Department of Physics and Chemistry, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
Urban
Christian
C
Merten
Nicole
N
Liebscher
Kathrin
K
Karlsen
Kasper K
KK
Hamacher
Alexandra
A
Spinrath
Andreas
A
Bond
Andrew D
AD
Drewke
Christel
C
Ullrich
Susanne
S
Kassack
Matthias U
MU
Kostenis
Evi
E
Ulven
Trond
T
D000818:Animals; D002934:Cinnamates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D005947:Glucose / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000819:agonists*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013997:Time Factors
D002934:Cinnamates; C473034:FFAR1 protein, human; C473036:Ffar1 protein, mouse; C473035:G-protein-coupled receptor 40, rat; D007328:Insulin; D043562:Receptors, G-Protein-Coupled; D005947:Glucose